Pyridine → (S)-4-[(S)-1-Acetoxymethyl-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

HRID 655586Notes

Reaction equation

HRID 655586 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[CH2:8]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C@H:24]([CH2:36][OH:37])[CH2:25][CH2:26][N:27]2[CH2:34][CH2:33][C:30]3([CH2:32][CH2:31]3)[C@H:29]([OH:35])[CH2:28]2)[C:20](=[O:38])[C@@H:19]1[CH3:39])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N1C=CC=CC=1.C(NCC)C>>[CH2:8]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C@H:24]([CH2:36][O:37][C:1](=[O:3])[CH3:2])[CH2:25][CH2:26][N:27]2[CH2:34][CH2:33][C:30]3([CH2:32][CH2:31]3)[C@H:29]([OH:35])[CH2:28]2)[C:20](=[O:38])[C@@H:19]1[CH3:39])=[O:17])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 8021DiethylamineHCID 68537480(S)-4-[(S)-3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-propyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester2×

Product 1

HCID 67080089(S)-4-[(S)-1-Acetoxymethyl-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl esterYield 72%

Procedure

Acetic anhydride (42 mg, 0.41 mmol) was added at 0° C. to a solution of (S)-4-[(S)-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-propyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (intermediate 39; 182 mg, 0.41 mmol) and pyridine (32 mg, 0.41 mmol). The ice bath was removed, then after 16 h excess reagent was destroyed by addition of diethylamine (15 mg, 0.21 mmol). After evaporation of volatile material, chromatography (SiO2; dichloromethane to dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) produced the title compound (143 mg, 72%). Colorless gum, MS (ISP)=488.4 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. customAfter evaporation of volatile material, chromatography (SiO2; dichloromethane to dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25)

Sources & evidence

ORD record
ord-f022c6c011eb4d32946eca5385274bdf
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

Loading…